The investigators suspect that significant degrees of iron overload in subjects with SCD result in decreased red cell survival, abnormal endothelial function and markedly dysregulated autonomic function. Furthermore, the investigators anticipate that the magnitude of these effects is proportional not only to the magnitude of total body iron stores but also to the duration of exposure to the high iron levels in tissues.

Treatment starting dose of 20mg/kg/day based on subjects baseline LIC (liver iron concentration) and gradually escalate the dose to a maximum of 35 mg/kg/day based upon toxicity. Duration is up to a max of 12 months.

Other Name: Exjade

Detailed Description:

Patients with sickle cell anemia often require blood transfusion as part of the treatment for their disease. Since each teaspoon of packed red blood cells contains about 5 mg of iron and humans have no way to get rid of excess iron, the levels of iron in sickle cell patients increase rapidly with each transfusion. Too much iron is extremely dangerous and causes damage to blood vessels, red blood cells, liver, hormone producing glands and heart. It is very difficult to know what damage due to iron overload in sickle cell patients because the sickle cell disease itself causes organ damage to the same organs affected by iron.

The purpose of this project is to demonstrate that iron overload significantly increases the morbidity of sickle cell disease and that treatment of the iron overload with Exjade® prevents or attenuates iron-related morbidity. To accomplish this we will screen sickle cell patients with a history of many blood transfusions to see if they have high iron levels. Then we will treat the patients who have very high iron levels with a drug which will remove the iron. Only patients with a very high iron level will be eligible for the treatment. These patients will have been transfused many times before but cannot currently be on blood transfusions. Before we start the treatment we will test the level of anemia, how fast the red cells are being destroyed, how well their blood vessels work and how well their heart works. When the treatment is over, we will repeat these tests and see if there is an improvement.

To qualify for this study, you must carry the diagnosis of sickle cell anemia and you must have received 10 or more blood transfusions in your life. You also cannot currently be on a regular transfusion program where you are getting blood transfusions regularly planned more than three times a year.

Patients with iron overload from repeated blood transfusion, as defined by one of the following:

For patients greater then 16 years old receiving simple transfusions: estimated lifetime history of receipt of at least 100 ml/kg or 15 adult units of packed red blood cells, OR

For patients equal to or less then 16 years old receiving simple transfusions: estimated lifetime history of receipt of at least 100 ml/kg of packed red blood cells, OR

For any patient: liver iron content equal/greater then 3 mg Fe/g dw as measured by biopsy or magnetic resonance imaging who have not been adequately chelated since that measurement, OR

a serum ferritin equal/greater then 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year. Samples must be obtained in the absence of concomitant infection

Life expectancy equal/greater then 12 months

Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)

AST or ALT greater then 250 U/L during screening (patients may be re-screened at a later date if the cause of the elevation is known to be due to a transient process).

Patients receiving currently on chelation will be asked to stop for one week before starting or restarting Exjade. (a equal/greater then 1 week washout period prior to first dose of study drug is required)

History of HIV positive test result (ELISA or Western blot)

History of drug or alcohol abuse within the 12 months prior to enrollment

Patients who received treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days or are planning to receive other investigational drugs while participating in the study

Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug

History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00981370